By Science History Institute on Thursday, October 25th, 2018
QESP Editors Note: An October 15, 2018 article in The Conversation, Boyer Lectures: gene therapy is still in its infancy but the future looks promising, brings another reminder of forgotten female scientists.
In 1953, four scientists co-discovered the double-helix structure of DNA, which formed the basis for modern biotechnology. In 1962 the three males, Watson, Crick and Franklin jointly received the Nobel Prize in Physiology or Medicine. The female, Rosalind Franklin (the only one who had any degrees in chemistry), had died in 1958 and although Watson recommended a posthumous award, none was made. The Royal Society Rosalind Franklin Award was established in 2003 and is awarded annually by the Royal Society to a woman for an outstanding work in any field of Science, technology, engineering, and mathematics (STEM). The Science History Institute gives a summary of the original research, including a short video, see James Watson, Francis Crick, Maurice Wilkins, and Rosalind Franklin. The original can be found here https://www.sciencehistory.org/historical-profile/james-watson-francis-crick-maurice-wilkins-and-rosalind-franklinhttps
At King’s College London, Rosalind Franklin obtained images of DNA using X-ray crystallography, an idea first broached by Maurice Wilkins. Franklin’s images allowed James Watson and Francis Crick to create their famous two-strand, or double-helix, model.
In 1962 Watson (b. 1928), Crick (1916–2004), and Wilkins (1916–2004) jointly received the Nobel Prize in Physiology or Medicine for their 1953 determination of the structure of deoxyribonucleic acid (DNA). Wilkins’s colleague Franklin (1920–1958), who died from cancer at the age of 37, was not so honored. The reasons for her exclusion have been debated and are still unclear. There is a Nobel Prize stipulation that states “in no case may a prize amount be divided between more than three persons.” The fact she died before the prize was awarded may also have been a factor, although the stipulation against posthumous awards was not instated until 1974.
The molecule that is the basis for heredity, DNA, contains the patterns for constructing proteins in the body, including the various enzymes. A new understanding of heredity and hereditary disease was possible once it was determined that DNA consists of two chains twisted around each other, or double helixes, of alternating phosphate and sugar groups, and that the two chains are held together by hydrogen bonds between pairs of organic bases—adenine (A) with thymine (T), and guanine (G) with cytosine (C). Modern biotechnology also has its basis in the structural knowledge of DNA—in this case the scientist’s ability to modify the DNA of host cells that will then produce a desired product, for example, insulin.
The background for the work of the four scientists was formed by several scientific breakthroughs: the progress made by X-ray crystallographers in studying organic macromolecules; the growing evidence supplied by geneticists that it was DNA, not protein, in chromosomes that was responsible for heredity; Erwin Chargaff’s experimental finding that there are equal numbers of A and T bases and of G and C bases in DNA; and Linus Pauling’s discovery that the molecules of some proteins have helical shapes—arrived at through the use of atomic models and a keen knowledge of the possible disposition of various atoms.
Of the four DNA researchers, only Rosalind Franklin had any degrees in chemistry. She was born into a prominent London banking family, where all the children—girls and boys—were encouraged to develop their individual aptitudes. She attended Newnham College, one of the women’s colleges at Cambridge University. She completed her degree in 1941 in the middle of World War II and undertook graduate work at Cambridge with Ronald Norrish, a future Nobel laureate. She resigned her research scholarship in just one year to contribute to the war effort at the British Coal Utilization Research Association. There she performed fundamental investigations on the properties of coal and graphite. She returned briefly to Cambridge, where she presented a dissertation based on this work and was granted a PhD in physical chemistry. After the war, through a French friend, she gained an appointment at the Laboratoire Centrale des Services Chimiques de l’Etat in Paris, where she was introduced to the technique of X-ray crystallography (see video on this page) and rapidly became a respected authority in this field. In 1951 she returned to England to King’s College London, where her charge was to upgrade the X-ray crystallographic laboratory there for work with DNA.
King’s College London and Horace Freeland Judson
Already at work at King’s College was Maurice Wilkins, a New Zealand–born but Cambridge-educated physicist. As a new PhD he worked during World War II on the improvement of cathode-ray tube screens for use in radar and then was shipped out to the United States to work on the Manhattan Project. Like many other nuclear physicists, he became disillusioned with his subject when it was applied to the creation of the atomic bomb; he turned instead to biophysics, working with his Cambridge mentor, John T. Randall—who had undergone a similar conversion—first at the University of St. Andrews in Scotland and then at King’s College London. It was Wilkins’s idea to study DNA by X-ray crystallographic techniques, which he had already begun to implement when Franklin was appointed by Randall. The relationship between Wilkins and Franklin was unfortunately a poor one and probably slowed their progress.
Meanwhile, in 1951, 23-year-old James Watson, a Chicago-born American, arrived at the Cavendish Laboratory in Cambridge. Watson had two degrees in zoology: a bachelor’s degree from the University of Chicago and a doctorate from Indiana University, where he became interested in genetics. He had worked under Salvador E. Luria at Indiana on bacteriophages, the viruses that invade bacteria in order to reproduce—a topic for which Luria received a Nobel Prize in Physiology or Medicine in 1969. Watson went to Denmark for postdoctoral work, to continue studying viruses and to remedy his relative ignorance of chemistry. At a conference in the spring of 1951 at the Zoological Station at Naples, Watson heard Wilkins talk on the molecular structure of DNA and saw his recent X-ray crystallographic photographs of DNA. He was hooked.
© A. Barrington Brown.
Watson soon moved to the Cavendish Laboratory, where several important X-ray crystallographic projects were in progress. Under the leadership of William Lawrence Bragg, Max Perutz was investigating hemoglobin and John Kendrew was studying myoglobin, a protein in muscle tissue that stores oxygen. (Perutz and Kendrew received the Nobel Prize in Chemistry for their work in the same year that the prize was awarded to the DNA researchers—1962.) Working under Perutz was Francis Crick, who had earned a bachelor’s degree in physics from University College London and had helped develop radar and magnetic mines during World War II. Crick, another physicist in biology, was supposed to be writing a dissertation on the X-ray crystallography of hemoglobin when Watson arrived, eager to recruit a colleague for work on DNA. Inspired by Pauling’s success in working with molecular models, Watson and Crick rapidly put together several models of DNA and attempted to incorporate all the evidence they could gather. Franklin’s excellent X-ray photographs, to which they had gained access without her permission, were critical to the correct solution. The four scientists announced the structure of DNA in articles that appeared together in the same issue of Nature.
Then they moved off in different directions. Franklin went to Birkbeck College, London, to work in J. D. Bernal’s laboratory, a much more congenial setting for her than King’s College. Before her untimely death from cancer she made important contributions to the X-ray crystallographic analysis of the structure of the tobacco mosaic virus, a landmark in the field. By the end of her life she had become friends with Francis Crick and his wife and had moved her laboratory to Cambridge, where she undertook dangerous work on the poliovirus. Wilkins applied X-ray techniques to the structural determination of nerve cell membranes and of ribonucleic acid (RNA)—a molecule that is associated with chemical synthesis in the living cell—while rising in rank and responsibility at King’s College. Watson’s subsequent career eventually took him to the Cold Spring Harbor Laboratory (CSHL) of Quantitative Biology on Long Island, New York, where as director from 1968 onward he led it to new heights as a center of research in molecular biology. From 1988 to 1992 he headed the National Center for Human Genome Research at the National Institutes of Health. Afterward he returned to CSHL, from which he retired in 2007. During Crick’s long tenure at Cambridge, he made fundamental contributions to unlocking the genetic code. He and Sydney Brenner demonstrated that each group of three adjacent bases on a single DNA strand codes for one specific amino acid. He also correctly hypothesized the existence of “transfer” RNA, which mediates between “messenger” RNA and amino acids. After 20 years at Cambridge, with several visiting professorships in the United States, Crick joined the Salk Institute for Biological Studies in La Jolla, California.
In 2005 James Watson was honored with the Othmer Gold Medal from the Chemical Heritage Foundation, now the Science History Institute, for his scientific talent, which has given the world a new intellectual understanding of the nature of life, making possible modern biotechnology and a better life for all mankind.